Different modeling approaches in the simulation of extrinsic coagulation factor X activation: limitations and areas of applicability

Blood coagulation is a complex network of proteolytic reactions in the blood plasma that results in fibrin clot formation. Proteolytic reactions on the phospholipid membrane surface play central role in this process. One particularly important example is FX activation by the extrinsic tenase (VIIa/TF). In this study we constructed three mathematical models of FX activation by VIIa/TF: A) a homogeneous "well-mixed" model, B) a two-compartment "well-mixed" model, C) a heterogeneous model with diffusion, to investigate the importance of inclusion of each complexity level. Additionally, the model of a vesicle in fluid flow was constructed. In this report the comparison of models in flow and non-flow conditions will be provided and conditions in which different levels of complexity were important will be determined. Additionally, the rate-limiting reaction stages and preferential FX delivery pathways to VIIa/TF will be determined in different conditions. We also proposed the experimental setting for the direct determination whether the FX binding to the membrane was a collision-limited or non-collision-limited process.